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Searching for Causes of Infertility: From Pathophysiologic Mechanisms to Therapeutic Strategies

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Editorial: Searching for causes of infertility: from pathophysiologic mechanisms to therapeutic strategies
Editorial26 June 2024
Editorial: Searching for causes of infertility: from pathophysiologic mechanisms to therapeutic strategies

Reproductive disorders are global health problems affecting millions of people worldwide. In humans, infertility is indeed a very serious disease that disturbs also mental health. In animals, it is not such a big problem, unless it involves, i.e., extinct species or precious specimens for the environment, farming, forestry, etc. In both humans and animals, it reflects abnormalities at many levels of the very complicated fertilization process. The search for the causes of the lack of offspring focuses primarily on the gametes themselvestheir fusion is the most important step in the fertilization process. The health of gametes depends on so many factors that it seems improbable that we reproduce.The discovery of new pathophysiological mechanisms affecting fertilization is a continuous process forced by the progress of methods. The innovative techniques used, e.g., advanced genomic analysis and functional experiments, provide robust evidence and insights into the genetic basis of reproductive health. Animal models greatly help to study of the fertilization process mechanisms.The investigation of genetic factors is currently the most promising type of biological research. Here, we recommend a collection of interesting publications on reproductive disorders, cervical cancer and male infertility. We hope that cognition of specific genetic variants and an understanding of the mechanisms involved in reproduction will refine the choice of therapies and contribute to global improvements in human and animal reproductive health.Three publications in this collection deal with the most serious dysfunctions of the female reproductive tract related to endometriosis, premature expiration of ovarian function, and cervical cancer. Studies of genetic variants indicate new polymorphisms that are candidates as potential biomarkers and could become new therapeutic targets. The publication by Chen et al. [Chen K, et al. 2022] concerns genetic polymorphisms in the world's most common cervical cancer in women. The authors investigated the association between specific genetic variations (SNPs) in microRNA genes involved in the PI3K/Akt signaling pathway and susceptibility to cervical cancer. Numerous researchers have pointed out that these dysregulated microRNAs could play an important role in cervical cancer development [Hillyar et al., 2023;Shen et al., 2020]. Some of the stage-specific microRNAs can also be used as biomarkers for cancer classification and monitoring the progression of cervical cancer [Causin et al., 2021]. Chen showed that rs107822 of miR-219a and rs2292832 of miR-149 were associated with cervical cancer risk, indicating a potential role of microRNAs in cervical cancer development. They predicted that miR-219a could target integrins (ITGA and ITGB) that participate in the activation of the PI3K/Akt signaling pathway. Thus, the function of these two SNPs in cervical cancer development should be investigated and verified in the future.In the paper of Wan et al. [Wan Z et al., 2023] the association between three WTAP (Wilms tumor 1-associated protein) gene polymorphisms and ovarian endometriosis risk in Chinese women was addressed. Results indicated that specific WTAP variants may increase susceptibility to ovarian endometriosis among Chinese women. They found that the rs1853259 G variant genotypes significantly increased, whereas the rs7766006 T variant decreased the association with ovarian endometriosis risk and were correlated with the WTAP expression level.Premature ovarian insufficiency is characterized by early loss of ovarian function before the age of 40 years. This disease has genetic basis. The relationship between novel CLPP (caseinolytic mitochondrial matrix peptidase proteolytic subunit) gene variation and premature ovarian insufficiency was investigated by Yuan et al. [Yuan X et al. 2023]. Results suggested that novel CLPP gene variant affects mitochondrial function and triggers granulosa cell apoptosis, potentially contributing to the pathogenesis of premature ovarian insufficiency. Women's health is important not only for procreation but also for the health of the offspring [Suszyńska-Zajczyk J et al., 2024]. Suszynska-Zajczyk et al. investigated the effects of maternal hyperhomocysteinemia induced by a high-methionine diet on the health of their offspring. Elevated homocysteine levels, are a known risk factor for cardiovascular, renal, and neurological diseases as well as pregnancy complications. Results suggested sex-dependent effects on cognition, muscle strength, and breeding outcomes in offspring. A high-metionine diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by hyperhomocysteinemia during embryonic development.Men's health and the disturbances on the reproductive process are presented the next two publications. Qureshi S et al. [Qureshi S et al., 2023] used whole-exome and genome sequencing to identify novel, clinically significant variants in testis-expressed gene 15 (TEX15) in unrelated men with spermatogenic failure (oligozoospermia, nonobstructive azoospermia). The authors found that recessive loss-of-function TEX15 mutations are associated with spermatogenic failures (meiotic double-strand break repair) in humans and a knockout male mice model. Lu S et al. investigated the association of sleep traits with male fertility [Lu S et al., 2024], such as the relationship between sleep-related traits (chronotype, sleep duration, insomnia, snoring, dozing, daytime nap, oversleeping, and undersleeping), abnormal sperm or bioavailable testosterone levels using Mendelian randomization analysis. Results suggested a potential link between genetically predicted chronotype and testosterone levels, but no significant association was observed between other sleep traits and male fertility. The authors point out that the human biological clock may be important in reducing the risk of male infertility.A common topic among all listed studies is the investigation of genetic factors and their impact on various aspects of reproductive health and disease. Using advanced genomic techniques, these studies explored the role of genetic variations (single nucleotide polymorphisms (SNPs) or gene mutations) in conditions such as: cervical cancer, male fertility, spermatogenic failure, premature ovarian insufficiency, endometriosis, and hyperhomocysteinemia-induced deficits in offspring. They also highlighted the importance of understanding the genetic basis of reproductive disorders for improving diagnosis, prognosis, and potential therapeutic interventions. In summary, genetic factors play a significant role in the development and progression of various reproductive disorders, and studying these factors can provide valuable insights into their underlying mechanisms and potential clinical implications [Nagirnaja et al., 2022;Malcher et al., 2022;Turkyilmaz et al., 2022]. Despite focusing on different conditions, all studies investigated how genetic variations contribute to disease susceptibility or reproductive health outcomes. Each study contributes valuable insights to its respective field, highlighting the complex interplay among genetics, environmental factors, and disease susceptibility or reproductive health.

2,079 views

ORIGINAL RESEARCH
17 March 2023
CLPP inhibition triggers apoptosis in human ovarian granulosa cells via COX5A abnormality–Mediated mitochondrial dysfunction
Xiong Yuan, 8 more and Jie Wu

5,798 views

18 citations

ORIGINAL RESEARCH
22 February 2024
Association of sleep traits with male fertility: a two-sample Mendelian randomization study
Shikuan Lu, 5 more and Peihai Zhang

8,115 views

11 citations

ORIGINAL RESEARCH
10 May 2023
Genomic study of TEX15 variants: prevalence and allelic heterogeneity in men with spermatogenic failure
Sidra Qureshi, 15 more and Alexander N. Yatsenko

6,456 views

10 citations

BRIEF RESEARCH REPORT
15 March 2024
Diet-induced hyperhomocysteinemia causes sex-dependent deficiencies in offspring musculature and brain function
Joanna Suszyńska-Zajczyk, 2 more and Hieronim Jakubowski

3,436 views

8 citations

ORIGINAL RESEARCH
14 April 2022
Genetic Polymorphisms in microRNA Genes Targeting PI3K/Akt Signal Pathway Modulate Cervical Cancer Susceptibility in a Chinese Population
Kerong Chen, 8 more and Li Shi

3,995 views

7 citations

SYSTEMATIC REVIEW
26 April 2024
The landscape of genetic variations in non-syndromic primary ovarian insufficiency in the MENA region: a systematic review
Asma Allouch, 2 more and Atiyeh M. Abdallah

4,668 views

5 citations

ORIGINAL RESEARCH
13 October 2023
WTAP gene variants and susceptibility to ovarian endometriosis in a Chinese population
Zixian Wan, 9 more and Wenfeng Hua

2,705 views

3 citations